The goal of this investigation is to develop an animal model to study the role of abnormal mechanical loads in articular cartilage degeneration, particularly that analogous to osteoarthritis (OA) of the knee. The proposed model consists of a mechanical varus loading device (VLD) that is fixed to the hind limb of a New Zealand White rabbit. The VLD applies a varus moment of known magnitude to the knee while allowing normal joint function. This causes a quantifiable increase in tibio-femoral contact load, AP, in the medial joint compartment. The advances made with this new approach are that these load alterations can be modified or removed at any time, and that iatrogenic trauma is minimized because no intra-articular surgery is needed. At this stage, this work is considered exploratory because, while there exists an apparent corollary from clinical experience that aberrant mechanical overload contributes to loss of cartilage integrity, the exact empirical nature of the requisite overload is not known. Before proceeding with animal studies that are necessary to understand interventions that will either exacerbate or retard degenerative processes, we need to be confident that a particular chronic mechanical burden reliably initiates cartilage degeneration processes which are not self-mitigating. The study will test the primary hypothesis: the level of cartilage degeneration (as quantified by histological scoring) is dependent on the magnitude and duration of varus load applied to the knee. Additional measures of cartilage material properties and cartilage metabolism (as quantified by assays of CPU, C2C, and CS-846) will be explored for their dependence on the magnitude and duration of varus load applied to the knee. Currently, there is no model available to study the onset and early progression of OA produced by chronic abnormal loading such as occurs with joint malalignment. Our work will lead to a new model that will have the capability to study the early changes that occur in the degenerative process with a direct link to humans. [unreadable] [unreadable] [unreadable]